Dynamics of Respiratory Infections
Our research
Microbiome, immune response and pathogenesis in the lung
The respiratory microbiome is a central, but as yet poorly understood, component of lung homeostasis. It contributes significantly to the maintenance of the basic immunological tone, to colonization resistance against pathogens and to the control of inflammatory processes. In contrast to the gut microbiome, however, the microbial communities of the lower respiratory tract have hardly been characterized to date - especially with regard to their functional role in health and disease.
A major reason for this lies in the methodological challenges: The microbial biomass in the lungs is low and the samples - e.g. from bronchoalveolar lavage - contain a high proportion of human DNA. In addition, there is a lack of standardized methods for the reliable analysis of non-bacterial microbes such as fungi (mycobiome) and viruses (virome). To date, there is a lack of comparative studies on the performance of different sequencing approaches, primer specificities and protocols for the analysis of microbial signatures from the lung.
Our research group is uniquely positioned at the interface of clinical infection medicine and translational microbiome research - as part of the Clinic for Pneumology and Infectiology at Hannover Medical School (MHH) and at the same time as the research group “Dynamics of Respiratory Infections (DINF)” at the Helmholtz Centre for Infection Research (HZI) in Braunschweig.
This dual anchoring enables direct feedback between clinical observation and basic scientific analysis. This structure allows us to transfer patient material and clinical questions into experimental systems in a targeted manner - and, conversely, to reflect molecular findings directly back into diagnostic or therapeutic applications. This makes it an ideal model for translational infection research with a focus on lung infections from the clinic to the laboratory and back.
We use state-of-the-art sequencing technologies - including amplicon-based ITS and 16S sequencing, shotgun metagenomics and long-read technologies - to enable the most comprehensive coverage of microbial communities possible. In addition, we develop computational evaluation strategies to reliably identify microbial signatures even with low biomass and a high proportion of human DNA. A particular focus is on the methodological development of the fungal components (mycobiome) of the respiratory microbiome, whose functional role in microbial networks and in the interaction with human cells is still largely unknown.
Our aim is to comprehensively characterize the microbial ecosystems of the lung and to better understand their role in the pathogenesis of respiratory diseases, such as community-acquired or nosocomial pneumonia. The focus is on classical pathogens such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli, as well as less studied commensals such as Streptococcus mitis, Prevotella spp., Moraxella catarrhalis and Haemophilus influenzae, which potentially exert immunomodulatory functions. In addition, we analyze the functional integration of fungal species - in particular Candida spp. and Aspergillus spp. - into the microbial communities of the lung and their interactions with bacterial microbes and host cells.
For functional analysis, we use advanced experimental platforms, including air-liquid interface (ALI) cultures, lung-on-chip systems, patient-derived lung tissue slices (PCLS) and human lung organoids. These models allow us to study the interactions between microorganisms, respiratory epithelium and alveolar macrophages in an immunologically relevant context.
In the long term, our research aims not only to better understand the microbial signature and dynamics in the lung, but also to harness them for clinical diagnostics and new therapeutic strategies - for example through targeted microbiome regulation, the identification of diagnostic markers or innovative approaches to the prevention and treatment of respiratory infections.
Our work is based on a range of methodological approaches, including proteomics, transcriptomics, microbiological analyses, and molecular biology. Air-liquid interface (ALI) cultures of primary lung epithelial cells are a central model used to study cellular and molecular interactions between host and pathogen. Additionally, we utilize precision-cut lung slices (PCLS) as an ex vivo model, which preserves tissue architecture and enables physiologically relevant investigations of pathogen dynamics and host responses. Using 16S rRNA and metagenomic sequencing, we study the composition and function of the lung microbiome under healthy and diseased conditions.
Our aim is to identify the molecular mechanisms driving pulmonary infections and to develop innovative therapeutic strategies to modulate the lung microbiome and immune responses.
We are committed to advancing new approaches for innovative strategies to improve the prevention and treatment of respiratory infections.
